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Purpose: Many factors have been associated with health-related quality of life (HRQOL), and researchers often have tried to rank these contributing factors. Variable importance quantifies the net independent contribution of each individual predictor in a set of predictors to the prediction accuracy of the outcome. This study assessed relative importance (RI) of selected contributing factors to respondents' physically unhealthy days (PUD), mentally unhealthy days (MUD), activity limitation days (ALD), and EuroQol EQ-5D index derived from the Healthy Days measures (dEQ-5D). Methods: Using data from the 2021 Behavioral Risk Factor Surveillance Systems (BRFSS), we estimated the RI of seven socio-demographics and seventeen chronic conditions and risk behaviors. A variable's importance was measured as the average increase in the coefficient of determination after adding the variable to all possible sub-models. Results: After controlling for socio-demographics, arthritis and no physical activity were the most important variables for PUD with a RI of 10.5 and 10.4, respectively, followed by depression (RI = 8.5) and COPD (RI = 8.3). Depression was the most important variable for MUD with RI = 23.0 while all other 16 predictors had a RI < 7.0. Similar results were observed for ALD and dEQ-5D: depression was the most important predictor (RI = 16.3 and 15.2, respectively), followed by no physical activity, arthritis, and COPD (RI ranging from 7.1 to 9.2). Conclusion: This study quantified and ranked selected contributing factors of HRQOL. Results of this analysis also can be used to validate HRQOL measures based on domain knowledge of HRQOL. [ABSTRACT FROM AUTHOR]